PV-10 Intralesional Injection vs Systemic Chemotherapy or Intralesional Oncolytic Viral Therapy for Treatment of Locally Advanced Cutaneous Melanoma
The goal of this study is to learn about the effectiveness of PV-10 compared with standard chemotherapy (dacarbazine or temozolomide) or with Imlygic (talimogene laherparepvec) in treating patients with melanoma. The safety and tolerability of PV-10 will also be studied.
Disease Group: Melanoma and other malignant neoplasms of skin
Treatment Agent: Dacarbazine
Treatment Location: Both at MDACC & and Other Sites
Sponsor: Provectus Biopharmaceuticals, Inc.
Primary Objective The primary objective of this study is to assess the effectiveness of intralesional (IL) PV-10 compared to the Investigator’s choice of systemic chemotherapy or intralesional oncolytic viral therapy in treating locally advanced cutaneous melanoma. Effectiveness will be assessed by comparison of progression-free survival (PFS) between all intent-to-treat (ITT) subjects in the two study treatment arms. Secondary Objectives This study will also include assessment and comparison of the two study treatment arms with respect to: Complete response rate (CRR). Duration of complete response. Overall survival (OS). Safety and tolerability. Exploratory Objectives Change from Baseline domain scores using the Skindex-16 instrument. Change in patient reported lesion pain score from Baseline. Change in patient reported pain medication use from Baseline. Change in Investigator assessed lesion bleeding from Baseline. Change in Investigator assessed lesion ulceration from Baseline. Change in Investigator assessed lesion infection from Baseline.
IRB Review and Approval Date: 04/26/2016
Recruitment Status: Open
Projected Accrual: 225
1) Age 18 years or older, male or female.
2) Histologically or cytologically confirmed melanoma. This can be based on the original diagnostic biopsy. No new biopsies are required.
3) Recurrent, satellite or in-transit locally advanced cutaneous or subcutaneous melanoma metastases (i.e., AJCC Stage IIIB, IIIC or Stage IV M1a with no active nodal metastases).
4) At least 1 cutaneous Target Lesion (each lesion >/= 10 millimeter (mm) in longest diameter or up to 5 lesions having a sum of longest diameters >10mm). Target Lesions should be at least 10 mm from any other lesion.
5) No lesion > 30 mm in longest diameter; and no more than 50 lesions.
6) Calculated required PV-10 dose </= 15 mL (based on total tumor burden).
7) Performance Status: Eastern Cooperative Oncology Group (ECOG) 0-2.
8) Failed, did not tolerate, or not a candidate for treatment with at least one immune checkpoint inhibitor (due to co-morbidities, pre-existing autoimmune disease, drug unavailability or standard of care).
9) Failed, did not tolerate, or not a candidate for targeted therapy with BRAF or combined BRAF/MEK inhibitors (i.e., BRAF V600 wild-type or due to drug unavailability or standard of care).
10) Clinical Laboratories: a) Absolute neutrophil count (ANC) >/= 1.5 x 10^9/L and platelet count >/=100 x 10^9/L. b) Creatinine </= 3 times the upper limit of normal (ULN). c) Estimated creatinine clearance (CrCl) or estimated glomerular filtration rate (eGFR) >/= 30 mL/min/1.73 m^2. d) Total bilirubin </= 3 times the upper limit of normal (ULN). e) Aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) </= 5 times the upper limit of normal (ULN). f) Lactate dehydrogenase (LDH) </= 2 times the upper limit of normal (ULN).
11) Thyroid function abnormality </= Common Terminology Criteria for Adverse Events (CTCAE) Grade 2.
12) Candidate for at least one comparator drug: Subjects must be candidates for at least one of the designated comparator drugs.
1) Presence or history of visceral metastasis.
2) Presence of active nodal metastases (e.g., radiologic or clinical evidence of current nodal disease).
3) Presence of more than 50 melanoma lesions.
4) Radiation Therapy to any Study Lesion within 6 weeks of initial study treatment.
5) Chemotherapy: a) Subjects who have received chemotherapy or other systemic cancer therapy within 4 weeks of initial study treatment (6 weeks for nitrosoureas or mitomycin). b) Subjects who have received regional chemotherapy (limb infusion or perfusion) within 12 weeks of initial study treatment.
6) Immunotherapy: Subjects who have received immunotherapy for cancer within 4 weeks of initial study treatment.
7) Local Treatment: Subjects who have received local treatment (e.g., surgery, cryotherapy, laser ablation) to any Study Lesion within 4 weeks of initial study treatment.
8) Anti-Tumor Vaccine: Subjects who have received anti-tumor vaccine therapy within 6 weeks of initial study treatment.
9) Investigational Agents: Subjects who have received investigational agents within 4 weeks of initial study treatment.
10) Concurrent or Intercurrent Illness: a) Subjects with impaired wound healing or other extremity complications due to diabetes mellitus whose Study Lesions are located in an extremity. b) Subjects with severe peripheral vascular disease (e.g., severe claudication [pain occurring after less than 200 meters of walking], rest pain, ischemic ulceration or gangrene) whose Study Lesions are located in an extremity. c) Subjects with significant concurrent or intercurrent illness, psychiatric disorders, or alcohol or chemical dependence that would, in the opinion of the Investigator, compromise their safety or compliance or interfere with interpretation of study results. d) Subjects with uncontrolled thyroid disease or cystic fibrosis. e) Subjects with clinically significant acute or unstable cardiovascular, cerebrovascular (stroke), renal, gastrointestinal, pulmonary, immunological, endocrine, or central nervous system disorders.
11) Pregnancy: a) Female subjects who are pregnant or lactating. b) Female subjects who have positive serum beta human chorionic gonadotropin (HCG) pregnancy test taken within 21 days of study treatment. c) Female subjects of child-bearing potential who are not using effective contraception (e.g., oral contraceptives, intrauterine devices, double barrier methods such as condoms and diaphragms, abstinence or equivalent measures).
12) Contraindication for all comparators: Subjects with contraindications to all of the designated comparator drugs.